Developing a translational murine-to-canine pathway for an IL-2/agonist anti-CD40 antibody cancer immunotherapy.

Human and canine sarcomas are difficult to treat soft tissue malignancies with an urgent need for new improved therapeutic options. Local recurrence rates for humans are between 10%-30%, and 30%-40% develop metastases. Outcomes for dogs with sarcoma vary with grade but can be similar. Pet dogs share the human environment and represent human cancer with genetic variation in hosts and tumours. We asked if our murine studies using genetically identical mice and cloned tumour cells were translatable to larger, genetically diverse domestic dogs with naturally occurring tumours, to (i) develop a canine cancer therapeutic, and (ii) to use as a translational pathway to humans. Our murine studies showed that intra-tumoral delivery of interleukin-2 (IL-2) plus an agonist anti-CD40 antibody (Ab) induces long-term curative responses ranging from 30% to 100%, depending on tumour type. We developed an agonist anti-canine-CD40 Ab and conducted a phase I dose finding/toxicology 3 + 3 clinical trial in dogs (n = 27) with soft tissue sarcomas on account of suitability for intratumoral injection and straightforward monitoring. Dogs were treated with IL-2 plus anti-CD40 antibody for 2 weeks. Three dose levels induced tumour regression with minimal side effects, measured by monitoring, haematological and biochemical assays. Importantly, our mouse and canine studies provide encouraging fundamental proof-of-concept data upon which we can develop veterinary and human immunotherapeutic strategies.

Polyostotic lymphoma with multiple pathological fractures in a six-month-old cat.

A 6-month-old female neutered domestic shorthair cat was examined for pain and swelling of the distal limbs. Swelling and malalignment of both carpi, dorsiflexion of the distal metatarsals and a mild, multicentric lymphadenopathy were detected on examination. Screening blood tests revealed a biclonal gammopathy, hypercalcemia and atypical leukocytes. Survey radiographs revealed lysis and proliferative changes within the physes. Multiple pathological physeal fractures were present, including the distal radii, metacarpal and metatarsal bones. No treatment was attempted and the patient was euthanased. Histopathology revealed infiltration by monomorphic round cells within the liver, spleen, kidney and bone marrow. Immunohistochemistry revealed strong reactivity to CD20. Clonality assays revealed clonal results for the B-cell loci, consistent with B-cell lymphoma. To the authors' knowledge this is the first report of polyostotic lymphoma with multiple pathological fractures in a cat. The predominantly distal distribution of osseous lesions is rarely reported in dogs and humans.

Vinblastine and prednisolone as adjunctive therapy for canine cutaneous mast cell tumors.

Twenty-seven dogs with inadequately excised, cutaneous mast cell tumors (MCT; 20 residual microscopic disease, seven marginal excision) were treated with a vinblastine and prednisolone chemotherapeutic protocol. Twenty dogs were available for follow-up examination after 12 months. One dog suffered local recurrence of the tumor, four dogs developed new cutaneous tumors, and one dog had both events. Fourteen dogs were free of MCT. There was no confirmed tumor-related mortality. Although toxicity from the chemotherapy was generally mild, one dog died of sepsis during treatment.